beta-ionone and Breast-Neoplasms

Topics: Animals; Apoptosis; Breast Neoplasms; Carcinoma, Hepatocellular; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Dose-Response Relationship, Drug; Down-Regulation; Female; Humans; Liver Neoplasms; Mammary Neoplasms, Experimental; MCF-7 Cells; Mice; NAD(P)H Dehydrogenase (Quinone); Norisoprenoids; Rats

To investigate the effect of cell proliferation in human breast cancer cells (MDA-MB 435), which has non-receptor of estrogen (Er), induced by beta-ionone. MDA-MB 435 cells were treated with different beta-ionone concentrations (25, 50, 100 and 200 micromol/L), with a negative control.. Such as curve of cell growth, cellular mitosis, the clone formatting, DNA synthesis, and western blotting for protein of PCNA and MAPK pathway were employed.. beta-ionone inhibited the cell proliferation, cellular mitosis, clone formatting and DNA synthesis and reduced expression of PCNA protein in MDA-MB 435 cells. The inhibitory frequency (IF) showed a dose-dependent responses as the concentrations of beta-ionone increased. Seven days after treatment with various concentrations of beta-ionone, as mentioned above, the inhibition rates were 45.65%, 71.24%, 81.53%, and 84.93%, respectively. Its IC50 value was 42.0 micromol/L for MDA-MB 435 cells. The IF from cellular mitosis of MDA-MB 435 cells treated by beta-ionone were - 34.57%-58.857% at 24 h and - 30.05%-75.12% at 48 h, from the clone formatting assay, - 4.44%-63.79% at 24 h and 6.42%-95.55% at 48 h, from DNA synthesis, 17.00%-57.56% at 24h and 62.25%-78.35% at 48 h. The further study was found that beta-ionone inhibited the expression of PCNA which to be related to cell cycle and reduced ERK, MEK-1 proteins expression and promoted the expression of JNK and MKP-1 proteins related to MAPK pathway in MDA-MB 435 cells.. beta-ionone could inhibit MDA-MB 435 cells proliferation by regulating MAPKs pathway. It may be one of the effects of beta-ionone in anticancer.

Topics: Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Female; Humans; MAP Kinase Kinase 1; Mitogen-Activated Protein Kinase 8; Mitogen-Activated Protein Kinase Kinases; Norisoprenoids; Receptors, Estrogen

To investigate the effect of cell proliferation induced by beta-ionone.. Human mammary cancer cells (MCF-7) were treated with various beta-ionone concentrations (25, 50, 100 and 200 mumol/L), with a negative control. Methods such as curve of cell growth, cellular mitosis, the cell clone formatting and DNA synthesis were employed.. beta-ionone inhibited the cell proliferation, cellular mitosis, the cell clone formatting and DNA synthesis. The inhibitory frequency (IF) showed a dose-dependent response as the concentrations of beta-ionone increased. Its IC50 value was 104 mumol/L for MCF-7 cells. The inhibitory frequency (IF) from cellular mitosis of MCF-7 treated by beta-ionone were - 12.88% - 68.67% at 24 h and 20.79% - 87.79% at 48 h, from the cell clone formatting of MCF-7 treated by beta-ionone, were - 14.11% - 65.18% at 24 h and 6.58% - 72.48% at 48 h, from DNA synthesis, 16.75% - 65.33% at 24 h and 35.10% - 81.89% at 48 h.. beta-ionone could inhibit the cell growth of MCF-7 cells and the mechanisms needs to be further studied.

Topics: Adenocarcinoma; Antineoplastic Agents; Breast Neoplasms; Cell Division; DNA, Neoplasm; Female; Humans; Norisoprenoids; Tumor Cells, Cultured

3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase catalyzes the formation of mevalonate, a precursor of cholesterol that is also required for cell proliferation. Mevalonate depletion results in a G1 phase cell cycle arrest that is mediated in part by impaired activity of cyclin-dependent kinase (CDK) 2, and decreased expression of positive regulators of G1 to S phase progression. Inhibition of mevalonate synthesis may, therefore, be a useful strategy to impair the growth of malignant cells. Plant isoprenoids, including beta-ionone and geraniol, have previously been shown to inhibit rodent mammary tumor development, and rodent and avian hepatic HMG-CoA reductase activity. We hypothesized that the putative anti-proliferative and cell cycle inhibitory effects of beta-ionone and geraniol on MCF-7 human breast cancer cells in culture are mediated by mevalonate depletion resulting from inhibition of HMG-CoA reductase activity. Flow cytometric analysis showed a G1 arrest in isoprenoid-treated MCF-7 cells, and also a G2/M arrest at higher concentrations of isoprenoids. These compounds minimally affected the growth of MCF-10F normal breast epithelial cells. Both beta-ionone and geraniol inhibited CDK 2 activity and dose-dependently decreased the expression of cyclins D1, E, and A, and CDK 2 and 4, without changing the expression of p21cip1 or p27kip1. Although both beta-ionone and geraniol also inhibited MCF-7 proliferation, only geraniol inhibited HMG-CoA reductase activity. While these effects were significantly correlated (r2=0.89, P <0.01), they were not causally related, since exogenous mevalonate did not restore growth in geraniol-inhibited cells. These findings indicate that mechanisms other than impaired mevalonate synthesis mediate the anti-proliferative and cell cycle regulatory effects of beta-ionone and geraniol in human breast cancer cells.

Topics: Acyclic Monoterpenes; Breast Neoplasms; CDC2-CDC28 Kinases; Cell Cycle; Cell Division; Cell Proliferation; Cyclin-Dependent Kinase 2; Dose-Response Relationship, Drug; G1 Phase; Gene Expression; Humans; Hydroxymethylglutaryl CoA Reductases; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Norisoprenoids; S Phase; Terpenes; Time Factors; Tumor Cells, Cultured

Diverse classes of phytochemicals initiate biological responses that effectively lower cancer risk. One class of phytochemicals, broadly defined as pure and mixed isoprenoids, encompasses an estimated 22,000 individual components. A representative mixed isoprenoid, gamma-tocotrienol, suppresses the growth of murine B16(F10) melanoma cells, and with greater potency, the growth of human breast adenocarcinoma (MCF-7) and human leukemic (HL-60) cells. beta-Ionone, a pure isoprenoid, suppresses the growth of B16 cells and with greater potency, the growth of MCF-7, HL-60 and human colon adenocarcinoma (Caco-2) cells. Results obtained with diverse cell lines differing in ras and p53 status showed that the isoprenoid-mediated suppression of growth is independent of mutated ras and p53 functions. beta-Ionone suppressed the growth of human colon fibroblasts (CCD-18Co) but only when present at three-fold the concentration required to suppress the growth of Caco-2 cells. The isoprenoids initiated apoptosis and, concomitantly arrested cells in the G1 phase of the cell cycle. Both suppress 3-hydroxy-3-methylglutaryl CoA reductase activity. beta-Ionone and lovastatin interfered with the posttranslational processing of lamin B, an activity essential to assembly of daughter nuclei. This interference, we postulate, renders neosynthesized DNA available to the endonuclease activities leading to apoptotic cell death. Lovastatin-imposed mevalonate starvation suppressed the glycosylation and translocation of growth factor receptors to the cell surface. As a consequence, cells were arrested in the G1 phase of the cell cycle. This rationale may apply to the isoprenoid-mediated G1-phase arrest of tumor cells. The additive and potentially synergistic actions of these isoprenoids in the suppression of tumor cell proliferation and initiation of apoptosis coupled with the mass action of the diverse isoprenoid constituents of plant products may explain, in part, the impact of fruit, vegetable and grain consumption on cancer risk.

Topics: Animals; Apoptosis; Breast Neoplasms; Caco-2 Cells; Cell Cycle; Cell Death; Chromans; DNA Fragmentation; Electrophoresis, Agar Gel; Female; Flow Cytometry; G1 Phase; HL-60 Cells; Humans; Lamin Type B; Lamins; Melanoma, Experimental; Mice; Norisoprenoids; Nuclear Proteins; Terpenes; Tumor Cells, Cultured; Vitamin E